Long term relief from arthritis could evolve from B-cell targeted treatments

Publication date:
Mar 13, 2006 2:41:00 PM

Long term relief for arthritis sufferers could be one step closer,
thanks to a study of B-cell targeted therapy published today. The study
from UCL reveals a major but hitherto poorly acknowledged role for
B-cells in the most common and severe form of arthritis to affect
younger people. By targeting B-cells, which are part of the body’s
immune system, it may be possible to break a key vicious cycle
underlying the disease.

The drug trial, led by UCL Professor Jonathan Edwards, published today in the New England Journal of Medicine,
explored the possibility of using a one-off drug treatment to banish
the symptoms of rheumatoid arthritis form the body for months or years,
with the ultimate aim of permanent relief, rather than relying on
continuous drug therapy.

Of 161 patients involved in the study, 43% of those receiving a
short course of B cell targeted therapy based on the drug rituximab
found arthritic symptoms such as joint pain, swelling and stiffness
were reduced by more than half as measured six months later, compared
with 13% in the control group who took conventional drugs only.

The study was designed to assess improvement over six months but it
was found that in many cases improvement was maintained for at least a
year, confirming pilot studies at UCL suggesting an average benefit
lasting over a year and sometimes as long as three years.

Previous laboratory research at UCL had led Professor Edwards and
colleague Dr Jo Cambridge to suggest that antibodies directed against
the body’s own proteins might not only cause inflammation in rheumatoid
arthritis but might also create a vicious cycle driving the disease on.
Antibodies are made by B-cells and the idea was put forward that
removing B-cells might cause the cycle, and the disease, to collapse.

Experience at UCL indicates that permanent relief from a single
course of treatment is not yet possible. However, the fact that
improvement can last for a period of years suggests that the approach
is on the right track. Moreover, studies from UCL and elsewhere in
other autoimmune diseases such as lupus are producing similar results.

Professor Edwards says: “This study provides clear evidence for the
importance of B-cells in rheumatoid arthritis, heralding a major shift
in our understanding of the disease.

“The cycle underlying autoimmune diseases such as rheumatoid
arthritis may be similar to a bug in a computer that makes it loop and
crash. B-cell targeted therapy is like rebooting the computer of your
immune system to sidestep the bug.

“As is often the case, if you have not removed the bug completely
the computer system may crash again. This seems to be where we are at
present, possibly because the current treatment does not remove more
than 80 to 90 per cent of B-cells, where the ideal treatment would
knock out 100 per cent of cells.

“The challenge is to break the cycle once and for all. Many
different B-cell targeted drugs are now in development and I am
optimistic that long term benefit from a single treatment is
achievable.

“People with arthritis desperately want to be free of painful,
sleepless nights and fatigue and stiffness in the day. They also want
to be free from the burden of long term drug treatment. This is what we
should be aiming for.”

Around a billion B-cells, or lymphocytes, are created every day by
the body’s immune system. B-cells generate antibodies to help fight
infections. Each B-cell makes a different antibody by shuffling its
antibody genes. B-cells that by chance make antibodies to the body’s
own proteins normally disappear. However, very rarely it seems that
they can set up the vicious cycle that allows them to grow and produce
damaging effects, known as autoimmunity.

Current B-cell targeted therapy works by knocking out ‘bad’ B-cells,
but also knocks out useful B-cells for a period of months. The effect
on ‘bad’ antibodies is greater than on useful antibodies but after
repeated treatments levels of useful antibodies may be reduced.

This suppression of the useful side of the immune system, with a
risk of infections, is a common problem with treatments for autoimmune
disease. Experience at UCL suggests that chest infection may be more
common during the months after B-cell targeted treatment.

For this reason further studies are needed to ensure the treatment
is as safe as possible. It is also an incentive to develop B cell
targeted therapy either to remove only disease-related B-cells or to
ensure that treatment is powerful enough to avoid the need for repeated
courses.

Over 350,000 people are affected by rheumatoid arthritis in the UK, which can start at any age from 15 onwards.

Professor Jonathan Edwards is Professor of Connective Tissue Medicine at University College London.

Notes for Editors

The NEJM study was funded by Roche Pharmaceuticals

For more information or to set up an interview, please contact Jenny
Gimpel at the University College London press office on +44 (0)20 7679
9739, e-mail j.gimpel@ucl.ac.uk.